platelet activating factor

Summary

Summary: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.

Top Publications

  1. Poisson C, Rollin S, Veronneau S, Bousquet S, Larrivée J, Le Gouill C, et al. Caveolae facilitate but are not essential for platelet-activating factor-mediated calcium mobilization and extracellular signal-regulated kinase activation. J Immunol. 2009;183:2747-57 pubmed publisher
    ..In conclusion, PAFR appears to localize within caveolae or lipid rafts in different cell types, and this location may be important for specific signaling events...
  2. Satoh K. [Plasma platelet-activating factor acetylhydrolase (PAF-AH) deficiency as a risk factor for stroke]. Brain Nerve. 2008;60:1319-24 pubmed
    ..Therefore plasma PAF-AH deficiency may be considered as a genetic risk factor for stroke, and recognition of this mutation in individuals may be useful for early initiation of preventive measures against stroke. ..
  3. Yang Y, Yin J, Baumgartner W, Samapati R, Solymosi E, Reppien E, et al. Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase. Eur Respir J. 2010;36:417-27 pubmed publisher
    ..These findings suggest rapid reduction in eNO production as a novel mechanism in the regulation of vascular permeability. ..
  4. Knapp S, von Aulock S, Leendertse M, Haslinger I, Draing C, Golenbock D, et al. Lipoteichoic acid-induced lung inflammation depends on TLR2 and the concerted action of TLR4 and the platelet-activating factor receptor. J Immunol. 2008;180:3478-84 pubmed
  5. Forsman H, Onnheim K, Andréasson E, Christenson K, Karlsson A, Bylund J, et al. Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production. PLoS ONE. 2013;8:e60169 pubmed publisher
    ..This represents a novel mechanism for amplification of neutrophil production of reactive oxygen species. ..
  6. Harayama T, Shindou H, Ogasawara R, Suwabe A, Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor. J Biol Chem. 2008;283:11097-106 pubmed publisher
    ..Each lyso-PAF AT biosynthesizes inflammatory and physiological amounts of PAF, depending on the cell type. These findings provide important knowledge for the understanding of the diverse pathological and physiological roles of PAF. ..
  7. Ma J, Harnett K, Behar J, Biancani P, Cao W. Signaling in TRPV1-induced platelet activating factor (PAF) in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2010;298:G233-40 pubmed publisher
    ..Capsaicin increased production of platelet activating factor (PAF), an important inflammatory mediator that acts as a chemoattractant and activator of immune cells...
  8. Jeong Y, Jung I, Lee C, Chang J, Chun S, Noh K, et al. The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock. PLoS ONE. 2009;4:e6503 pubmed publisher
    ..Taken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators. ..
  9. Tsantila N, Tsoupras A, Fragopoulou E, Antonopoulou S, Iatrou C, Demopoulos C. In vitro and in vivo effects of statins on platelet-activating factor and its metabolism. Angiology. 2011;62:209-18 pubmed publisher
    b>Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF...
  10. Sánchez F, Rana R, González F, Iwahashi T, Duran R, Fulton D, et al. Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability. J Biol Chem. 2011;286:30409-14 pubmed publisher
    ..Our results demonstrate that the presence of eNOS in the cytosol is necessary for PAF-induced hyperpermeability. Our data provide new insights into the dynamics of eNOS and eNOS-derived NO in the process of inflammation. ..

Detail Information

Publications62

  1. Poisson C, Rollin S, Veronneau S, Bousquet S, Larrivée J, Le Gouill C, et al. Caveolae facilitate but are not essential for platelet-activating factor-mediated calcium mobilization and extracellular signal-regulated kinase activation. J Immunol. 2009;183:2747-57 pubmed publisher
    ..In conclusion, PAFR appears to localize within caveolae or lipid rafts in different cell types, and this location may be important for specific signaling events...
  2. Satoh K. [Plasma platelet-activating factor acetylhydrolase (PAF-AH) deficiency as a risk factor for stroke]. Brain Nerve. 2008;60:1319-24 pubmed
    ..Therefore plasma PAF-AH deficiency may be considered as a genetic risk factor for stroke, and recognition of this mutation in individuals may be useful for early initiation of preventive measures against stroke. ..
  3. Yang Y, Yin J, Baumgartner W, Samapati R, Solymosi E, Reppien E, et al. Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase. Eur Respir J. 2010;36:417-27 pubmed publisher
    ..These findings suggest rapid reduction in eNO production as a novel mechanism in the regulation of vascular permeability. ..
  4. Knapp S, von Aulock S, Leendertse M, Haslinger I, Draing C, Golenbock D, et al. Lipoteichoic acid-induced lung inflammation depends on TLR2 and the concerted action of TLR4 and the platelet-activating factor receptor. J Immunol. 2008;180:3478-84 pubmed
  5. Forsman H, Onnheim K, Andréasson E, Christenson K, Karlsson A, Bylund J, et al. Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production. PLoS ONE. 2013;8:e60169 pubmed publisher
    ..This represents a novel mechanism for amplification of neutrophil production of reactive oxygen species. ..
  6. Harayama T, Shindou H, Ogasawara R, Suwabe A, Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor. J Biol Chem. 2008;283:11097-106 pubmed publisher
    ..Each lyso-PAF AT biosynthesizes inflammatory and physiological amounts of PAF, depending on the cell type. These findings provide important knowledge for the understanding of the diverse pathological and physiological roles of PAF. ..
  7. Ma J, Harnett K, Behar J, Biancani P, Cao W. Signaling in TRPV1-induced platelet activating factor (PAF) in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2010;298:G233-40 pubmed publisher
    ..Capsaicin increased production of platelet activating factor (PAF), an important inflammatory mediator that acts as a chemoattractant and activator of immune cells...
  8. Jeong Y, Jung I, Lee C, Chang J, Chun S, Noh K, et al. The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock. PLoS ONE. 2009;4:e6503 pubmed publisher
    ..Taken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators. ..
  9. Tsantila N, Tsoupras A, Fragopoulou E, Antonopoulou S, Iatrou C, Demopoulos C. In vitro and in vivo effects of statins on platelet-activating factor and its metabolism. Angiology. 2011;62:209-18 pubmed publisher
    b>Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF...
  10. Sánchez F, Rana R, González F, Iwahashi T, Duran R, Fulton D, et al. Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability. J Biol Chem. 2011;286:30409-14 pubmed publisher
    ..Our results demonstrate that the presence of eNOS in the cytosol is necessary for PAF-induced hyperpermeability. Our data provide new insights into the dynamics of eNOS and eNOS-derived NO in the process of inflammation. ..
  11. Liu W, Ding W, Gu H, Chen M, Hu J. Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antagonist. Neurosci Bull. 2007;23:271-6 pubmed
    ..LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.
  12. Burks A. Peanut allergy. Lancet. 2008;371:1538-46 pubmed publisher
    ..This Seminar looks at the changing epidemiology of this allergy--and theories as to the rise in prevalence, diagnosis, and management of the allergy, and potential new treatments and prevention strategies under development. ..
  13. Liu M, Zhu H, Li J, Garcia C, Feng W, Kirpotina L, et al. Group A Streptococcus secreted esterase hydrolyzes platelet-activating factor to impede neutrophil recruitment and facilitate innate immune evasion. PLoS Pathog. 2012;8:e1002624 pubmed publisher
  14. Patel M, Kurek C, Dong Q. The arachidonic acid pathway and its role in prostate cancer development and progression. J Urol. 2008;179:1668-75 pubmed publisher
    ..on prostate cancer and arachidonic acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet activating factor, prostaglandin and eicosanoid...
  15. Egea L, Gimenez R, Lúcia D, Modolell I, Badia J, Baldoma L, et al. Increased production of the ether-lipid platelet-activating factor in intestinal epithelial cells infected by Salmonella enteritidis. Biochim Biophys Acta. 2008;1781:270-6 pubmed publisher
    ..This response is Ca(2+)-dependent. ..
  16. Chini M, Tsoupras A, Mangafas N, Tsogas N, Papakonstantinou V, Fragopoulou E, et al. Effects of highly active antiretroviral therapy on platelet activating factor metabolism in naive HIV-infected patients: ii) study of the abacavir/lamivudine/efavirenz HAART regimen. Int J Immunopathol Pharmacol. 2012;25:247-58 pubmed
    ..This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART. ..
  17. Borthakur A, Bhattacharyya S, Alrefai W, Tobacman J, Ramaswamy K, Dudeja P. Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent. Inflamm Bowel Dis. 2010;16:593-603 pubmed publisher
    ..The proinflammatory effects of PAF play prominent roles in the pathogenesis of IBD and this pathway may present important targets for intervention in chronic inflammatory diseases of the intestine. ..
  18. Chen J, Yang L, Foulks J, Weyrich A, Marathe G, McIntyre T. Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesis. J Lipid Res. 2007;48:2365-76 pubmed
  19. Kuebler W, Yang Y, Samapati R, Uhlig S. Vascular barrier regulation by PAF, ceramide, caveolae, and NO - an intricate signaling network with discrepant effects in the pulmonary and systemic vasculature. Cell Physiol Biochem. 2010;26:29-40 pubmed publisher
  20. Claud E, Lu J, Wang X, Abe M, Petrof E, Sun J, et al. Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1191-200 pubmed publisher
    ..Our data suggest a novel mechanism of PAF-induced injury by which PAF induces intracellular acidosis via activation of the Ca(2+)-dependent Cl(-) channel ClC-3, resulting in apoptosis of IEC. ..
  21. van Zoelen M, Florquin S, Meijers J, de Beer R, de Vos A, de Boer O, et al. Platelet-activating factor receptor contributes to host defense against Pseudomonas aeruginosa pneumonia but is not essential for the accompanying inflammatory and procoagulant response. J Immunol. 2008;180:3357-65 pubmed
    ..Additionally, our results indicate that PAFR signaling is not essential for the induction of a local and systemic inflammatory and procoagulant response to Pseudomonas pneumonia. ..
  22. Vadas P, Gold M, Perelman B, Liss G, Lack G, Blyth T, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358:28-35 pubmed publisher
    ..The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported...
  23. Detopoulou P, Nomikos T, Fragopoulou E, Antonopoulou S, Kotroyiannis I, Vassiliadou C, et al. Platelet activating factor (PAF) and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure. Clin Biochem. 2009;42:44-9 pubmed publisher
    To evaluate platelet activating factor (PAF) levels, its metabolic enzymes activity and its associations with other inflammatory markers in heart failure (HF) patients...
  24. Giannattasio G, Lai Y, Granata F, Mounier C, Nallan L, Oslund R, et al. Expression of phospholipases A2 in primary human lung macrophages: role of cytosolic phospholipase A2-alpha in arachidonic acid release and platelet activating factor synthesis. Biochim Biophys Acta. 2009;1791:92-102 pubmed publisher
    ..Our results indicate that human macrophages express cPLA(2)-alpha, iPLA(2) and several sPLA(2)s. Cytosolic PLA(2)-alpha is the major enzyme responsible for lipid mediator production in human macrophages. ..
  25. McIntyre T, Prescott S, Stafforini D. The emerging roles of PAF acetylhydrolase. J Lipid Res. 2009;50 Suppl:S255-9 pubmed publisher
    ..The roles of these enzymes are manifold, and their separate and combined functions are now being addressed in model systems and clinical studies. ..
  26. Lu J, Pierce M, Franklin A, Jilling T, Stafforini D, Caplan M. Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis. Pediatr Res. 2010;68:225-30 pubmed publisher
    ..In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and because preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. ..
  27. Marotta D, Costa R, Motta E, Fernandes E, Medeiros R, Quintão N, et al. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw. Biochem Pharmacol. 2009;77:1223-35 pubmed
    ..They also support the concept that selective PAF receptor antagonists might constitute interesting targets for the development of new analgesic drugs. ..
  28. Lu J, Caplan M, Li D, Jilling T. Polyunsaturated fatty acids block platelet-activating factor-induced phosphatidylinositol 3 kinase/Akt-mediated apoptosis in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1181-90 pubmed publisher
  29. Liu J, Chen R, Marathe G, Febbraio M, Zou W, McIntyre T. Circulating platelet-activating factor is primarily cleared by transport, not intravascular hydrolysis by lipoprotein-associated phospholipase A2/ PAF acetylhydrolase. Circ Res. 2011;108:469-77 pubmed publisher
    ..Intravascular PAF has access to intracellular compartments. Inflammatory and proapoptotic phospholipids may accumulate in the circulation as transport is overwhelmed by substrates in hyperlipidemia. ..
  30. Howard K, Abdel Al M, Ditmyer M, Patel N. Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways. Inflamm Res. 2011;60:735-44 pubmed publisher
    ..PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent. The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways. ..
  31. Sahu R, Kozman A, Yao Y, Dasilva S, Rezania S, Martel K, et al. Loss of the platelet activating factor receptor in mice augments PMA-induced inflammation and cutaneous chemical carcinogenesis. Carcinogenesis. 2012;33:694-701 pubmed publisher
    ..This suggests that the platelet activating factor receptor (PAFR) acts to suppress chronic inflammation in response to other stimuli, such as barrier ..
  32. Seki M, Kosai K, Hara A, Imamura Y, Nakamura S, Kurihara S, et al. Expression and DNA microarray analysis of a platelet activating factor-related molecule in severe pneumonia in mice due to influenza virus and bacterial co-infection. Jpn J Infect Dis. 2009;62:6-10 pubmed
    ..These findings suggest that PAF and related molecules play important roles in fulminant pneumonia due to influenza virus infection, especially when severe bacterial pneumonia is complicated by co-infection with influenza virus. ..
  33. Tsoupras A, Chini M, Tsogas N, Fragopoulou E, Nomikos T, Lioni A, et al. Anti-platelet-activating factor effects of highly active antiretroviral therapy (HAART): a new insight in the drug therapy of HIV infection?. AIDS Res Hum Retroviruses. 2008;24:1079-86 pubmed publisher
    ..These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy. ..
  34. Tsoupras A, Papakyriakou A, Demopoulos C, Philippopoulos A. Synthesis, biochemical evaluation and molecular modeling studies of novel rhodium complexes with nanomolar activity against Platelet Activating Factor. J Inorg Biochem. 2013;120:63-73 pubmed publisher
    ..On the other hand, the octahedral rhodium(III) complexes 3-5 that cannot fit the ligand-binding domain, could potentially exhibit their activity at the extracellular domain of the receptor...
  35. Nasopoulou C, Tsoupras A, Karantonis H, Demopoulos C, Zabetakis I. Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism. Lipids Health Dis. 2011;10:213 pubmed publisher
    b>Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested...
  36. Jönsson F, Mancardi D, Kita Y, Karasuyama H, Iannascoli B, Van Rooijen N, et al. Mouse and human neutrophils induce anaphylaxis. J Clin Invest. 2011;121:1484-96 pubmed publisher
    ..These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans...
  37. Belanger C, Elimam H, Lefebvre J, Borgeat P, Marleau S. Involvement of endogenous leukotriene B4 and platelet-activating factor in polymorphonuclear leucocyte recruitment to dermal inflammatory sites in rats. Immunology. 2008;124:295-303 pubmed publisher
    ..Our results strongly support a role of both endogenous LTB(4) and PAF in regulating PMN trafficking to inflammatory sites in various experimental conditions. ..
  38. Corl C, Gandy J, Sordillo L. Platelet activating factor production and proinflammatory gene expression in endotoxin-challenged bovine mammary endothelial cells. J Dairy Sci. 2008;91:3067-78 pubmed publisher
    ..b>Platelet activating factor (PAF), interleukin 1 beta (IL-1 beta), IL-8, and intercellular adhesion molecule 1 (ICAM1) are among the ..
  39. Fragel Madeira L, Meletti T, Mariante R, Monteiro R, Einicker Lamas M, Bernardo R, et al. Platelet activating factor blocks interkinetic nuclear migration in retinal progenitors through an arrest of the cell cycle at the S/G2 transition. PLoS ONE. 2011;6:e16058 pubmed publisher
    Nuclear migration is regulated by the LIS1 protein, which is the regulatory subunit of platelet activating factor (PAF) acetyl-hydrolase, an enzyme complex that inactivates the lipid mediator PAF...
  40. Donado E, Izquierdo I, Pérez I, García O, Antonijoan R, Gich I, et al. No cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines. Br J Clin Pharmacol. 2010;69:401-10 pubmed publisher
    ..This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety. ..
  41. Knezevic I, Predescu S, Neamu R, Gorovoy M, Knezevic N, Easington C, et al. Tiam1 and Rac1 are required for platelet-activating factor-induced endothelial junctional disassembly and increase in vascular permeability. J Biol Chem. 2009;284:5381-94 pubmed publisher
  42. Kennedy M, Kabbani N, Lambert J, Swayne L, Ahmed F, Figeys D, et al. Srf1 is a novel regulator of phospholipase D activity and is essential to buffer the toxic effects of C16:0 platelet activating factor. PLoS Genet. 2011;7:e1001299 pubmed publisher
    ..Together, these findings implicate PLD as a potential neuroprotective target capable of ameliorating disruptions in lipid metabolism in response to accumulating oligomeric amyloid-???. ..
  43. Kihara Y, Yanagida K, Masago K, Kita Y, Hishikawa D, Shindou H, et al. Platelet-activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso-PAFAT axis. J Immunol. 2008;181:5008-14 pubmed
    ..These data suggest that PAF accumulation in the SC of EAE mice is profoundly dependent on the group IVA cytosolic PLA(2)/LysoPAFAT axis present in the infiltrating macrophages and activated microglia. ..
  44. Frost B, Jilling T, Caplan M. The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis. Semin Perinatol. 2008;32:100-6 pubmed publisher
    ..In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. ..
  45. Whitehead S, Hou W, Ethier M, Smith J, Bourgeois A, Denis R, et al. Identification and quantitation of changes in the platelet activating factor family of glycerophospholipids over the course of neuronal differentiation by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. Anal Chem. 2007;79:8539-48 pubmed
    ..Synthesis of the platelet activating factor (PAF) glycerophospholipid subclass is implicated in the control of neuronal differentiation and death...
  46. Kolovou V, Papakonstantinou V, Stamatakis G, Verouti S, Xanthopoulou M, Kolovou G, et al. Platelet activating factor levels and metabolism in Tangier disease: a case study. Lipids Health Dis. 2012;11:89 pubmed publisher
    ..In addition, PAF can be biosynthesized from the remodeling and the de novo pathways in which Lyso-platelet activating factor-acetyltransferase (Lyso-PAF-AT) and platelet activating factor-cholinephosphotransferase (PAF-CPT) are ..
  47. Tsoupras A, Fragopoulou E, Nomikos T, Iatrou C, Antonopoulou S, Demopoulos C. Characterization of the de novo biosynthetic enzyme of platelet activating factor, DDT-insensitive cholinephosphotransferase, of human mesangial cells. Mediators Inflamm. 2007;2007:27683 pubmed
    b>Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes...
  48. Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert D, et al. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009;123:342-51 pubmed publisher
    ..Resistance to digestion and dendritic cell activation by the major peanut allergen Ara h 1 are reported to contribute to its allergenicity...